The aims of the proposal are to design, prepare, and demonstrate new particulate polymeric separation media for application in the enhanced detection, analysis, or production of biologically active compounds. Unlike the commonly used silica beads, the new polymer beads will exhibit rugged chemical stability while versatility of their surface chemistries will be fine-tuned to allow their specific interaction with various uses of biopolymers, drugs, or metabolites. In particular, polymeric media for normal phase, hydrophilic interaction, or affinity chromatography, and chiral media optimized for the resolution of enantiomeric drugs be studied. The approach used will combine fine control over bead size, surface area and pore-size distribution, with the development of surface chemistries that are free of the interfering functionalities normally present in silica. Several families of bead polymers based both on commercially available and specialty monomers and crosslinkers will be used to prepare the size monodisperse beads. Once the beads have been prepared, their internal chemistry will be optimized for the target application using for example size-selective modification procedures to allow reversible interactions of large pores with proteins. Difficult bets such as lipids or saccharides will be selected to demonstrate the enhanced capabilities of the polymer beads. Chiral separation media are of great importance for the development of single enantiomer drugs. A combinatorial approach, coupled to a very fast screening method, will be used to develop highly optimized combinations of chiral selectors and tethering groups. In addition, the first libraries of chiral beads will be developed in which all three components (polymer support, chiral selector and tether) are optimized simultaneously for synergistic action. Overall, the new polymer beads developed under this proposal will contribute to enhance vastly both analytical and preparative capabilities in laboratories involved with analysis, clinical diagnostics, biotechnology, drug discovery, and pharmaceutical process optimization.